Sensorimotor gating in humans with tinnitus and hyperacusis

描述(由申请人提供)：这项关于检查患有耳鸣和听力亢进的人类的感觉运动门控的经典指标--声学惊厥反应(ASR)和脉冲前抑制(PPI)--的建议既重要又及时。其动机是：(I)几乎完全没有关于与人类耳鸣或听觉过敏有关的ASR或PPI的数据，尽管这些措施成功地客观化和阐明了也被认为涉及抑制和过度兴奋失败的各种其他情况，包括精神分裂症、强迫症和抽动症综合征，(Ii)动物模型中增强的ASR表明听力亢进，但缺乏验证这一假设的数据，以及(Iii)最近对动物耳鸣的间隙检测惊吓反射(GDSR)测试的兴趣激增，这还有待于在人类身上进行验证，并依赖于ASR和调节PPI的神经电路。拟议中的测量人类受试者的ASR、PPI和GDSR的实验将测试(1)是否可以从其他更深入研究的神经系统疾病中获得对耳鸣和听觉过敏机制的见解，而ASR和PPI已经很好地表征了这些情况；以及(2)被认为表明动物听力过敏和耳鸣的ASR和GDSR措施是否确实有效。这项拟议的工作对于理解临床耳鸣和听觉过敏至关重要，具体地说，是将其与这些日益普遍的疾病的潜在神经机制的动物数据联系起来。

DESCRIPTION (provided by applicant): This proposal to examine classic indicators of sensorimotor gating - the acoustic startle response (ASR) and prepulse inhibition (PPI) - in humans with tinnitus and hyperacusis is both important and timely. It is motivated by (i) the almost complete absence of data on either ASR or PPI in relation to human tinnitus or hyperacusis, despite the success of these measures in objectifying and elucidating a variety of other conditions also thought to involve failures of inhibition and over-excitation, including schizophrenia, obsessive compulsive disorder and Tourette's syndrome, (ii) suggestions that enhanced ASR in animal models indicates hyperacusis, but a lack of data testing this hypothesis and, (iii) the recent surge of interest in a gap-detection startle reflex (GDSR) test fo tinnitus in animals, which has yet to be validated in humans and is reliant on the ASR and neural circuitry mediating PPI. The proposed experiments measuring ASR, PPI and GDSR in human subjects will test (1) whether insights into the mechanisms of tinnitus and hyperacusis might be leveraged from other more heavily studied neurological conditions for which the ASR and PPI are already well-characterized, and (2) whether ASR and GDSR measures thought to indicate hyperacusis and tinnitus in animals actually do. The proposed work is crucial to understanding clinical tinnitus and hyperacusis and, specifically, relating it to animal data on th underlying neural mechanisms of these increasingly prevalent disorders.